Zeng C, Giantsoudi D, Grassberger C, Goldberg S, Niemierko A, Paganetti H, Trofimov A
Massachusetts General Hospital, Boston, MA.
Med Phys. 2012 Jun;39(6Part18):3832. doi: 10.1118/1.4735641.
Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and controlled distribution of proton's linear energy transfer (LET). We evaluate potential gain in therapeutic effect from delivery of daily inhomogeneous fractional dose distributions in pencil beam scanning proton therapy (PBS-PT).
For cases of prostate cancer, we considered a hypofractionated course of 20 fractions of 3 Gy (assuming α/β=1.5, the equivalent dose in 2-Gy fractions (ED2Gy) is 77.1 Gy). Two sets of dose distributions were planned using two opposed lateral fields to deliver a uniform dose: (1) in full-target plans (FTP) each beam targeted the entire gland (2) in split-target plans (STP), beams targeted only the respective proximal hemispheres (prostate split sagittally). Linear combinations of optimized beam intensity maps from FTP and STP, for a variety of mixing weights, were used to evaluate inhomogeneous fractional dose (IFD) distributions. IFD delivered doses boosting either hemisphere in alternating fractions, e.g., alternating between 40% and 160% of the nominal fractional dose (1.2-4.8 Gy). The equivalent uniform dose (EUD) was calculated for ED2Gy distributions. IFD plans were rescaled so that the EUD of rectum and bladder did not increase. LET distributions were calculated with Monte Carlo, and compared for different plans.
In the IFD courses, the whole prostate received a nearly uniform dose in every 2 fractions, however EUD was higher than in conventional FTP by up to 8%. Rectal EUD decreased by 2%, and bladder EUD was unchanged. The LET distributions of FTP and STP were distinctly different, thus, in IFD, LET depended strongly on the mixing weights.
In PBS-PT, modestly improved therapeutic outcome can be expected with delivery of inhomogeneous daily dose distributions, while administering the prescribed dose to target over the entire course. The biological effectiveness may be further enhanced by optimizing the LET distributions. The project was supported by the Federal Share of program income earned by Massachusetts General Hospital on C06 CA059267, Proton Therapy Research and Treatment Center.
通过大分割、局部剂量递增以及控制质子线性能量传递（LET）的分布，可以增强辐射的生物学效应。我们评估在笔形束扫描质子治疗（PBS-PT）中每日非均匀分次剂量分布所带来的潜在治疗效果增益。
对于前列腺癌病例，我们考虑了一个20次、每次3 Gy的大分割疗程（假设α/β = 1.5，2 Gy分次的等效剂量（ED2Gy）为77.1 Gy）。使用两个相对的侧野设计了两组剂量分布以给予均匀剂量：（1）在全靶区计划（FTP）中，每个射束靶向整个腺体；（2）在分割靶区计划（STP）中，射束仅靶向各自的近端半球（前列腺矢状面分割）。对于各种混合权重，使用来自FTP和STP的优化射束强度图的线性组合来评估非均匀分次剂量（IFD）分布。IFD在交替分次中给予剂量增强任一半球，例如，在标称分次剂量（1.2 - 4.8 Gy）的40%和160%之间交替。计算ED2Gy分布的等效均匀剂量（EUD）。对IFD计划进行重新缩放，以使直肠和膀胱的EUD不增加。用蒙特卡罗方法计算LET分布，并对不同计划进行比较。
在IFD疗程中，整个前列腺在每2次分次中接受几乎均匀的剂量，然而EUD比传统FTP高8%。直肠EUD降低2%，膀胱EUD不变。FTP和STP的LET分布明显不同，因此，在IFD中，LET强烈依赖于混合权重。
在PBS-PT中，在整个疗程中向靶区给予规定剂量的同时，给予非均匀每日剂量分布可预期适度改善治疗结果。通过优化LET分布，生物学有效性可能会进一步提高。该项目由马萨诸塞州总医院在C06 CA059267（质子治疗研究与治疗中心）项目收入中的联邦份额资助。
